A specific genetic mutation called BRAF V600E is found in some colorectal cancers and is linked to poor outcomes. While an FDA-approved drug combination — encorafenib + cetuximab — exists, only about one in five patients respond. Even among those who do, most eventually stop benefiting as the cancer develops resistance.

Dean, Jean M. Schmidt Chair, and Professor Jill Kolesar was among the researchers on the study “Inhibition of Fatty Acid Synthase Enhances Therapeutic Efficacy and Delays Acquired Resistance to BRAF-targeted Therapy in Colorectal Cancer,” published in Neoplasia, which investigated why and how cancer cells become resistant to BRAF-targeted drugs, focusing on a second-generation drug called PLX8394. 

They found that resistant cancer cells become more aggressive, with an increased ability to grow and invade surrounding tissue—making them harder to treat. These cells also ramp up fat (lipid) production, particularly through an enzyme called fatty acid synthase (FASN). Higher FASN activity appears to help cancer cells survive drug treatment. 

Importantly, when researchers added a FASN inhibitor (TVB3664) to BRAF-targeted therapy before resistance developed, it significantly delayed resistance by slowing cancer cell growth.

These findings suggest that starting combination therapy earlier—rather than waiting for resistance to emerge—could help patients benefit from treatment for longer. FASN may represent a promising new target in this hard-to-treat form of colorectal cancer.